tbuckley/cabot-search huggingface dataset:
Abstract 11902: Hypertension Severity Impacts Declines in Left Ventricular Ejection Fraction Among Women Receiving Adjuvant Chemotherapy for Breast Cancer (UPBEAT WF-97415)
Authors: Riya Garg, Nathaniel S O'Connell, Glenn J Lesser, Jennifer H Jordan, Arnethea L Sutton, Wendy Bottinor, Amy C Ladd, Ralph Dagostino, William G Hundley
Journal: Circulation (2022)

Introduction: AHA/ACC hypertension guidelines do not clearly address pharmacological treatment of increases in blood pressure (BP) in women receiving potentially cardiotoxic chemotherapy for treatment of breast cancer. Methods and Results: Magnetic resonance measures of left ventricular ejection fraction (LVEF) were performed in women with stage I-III breast cancer prior to and three months after initiating potentially cardiotoxic chemotherapy. Measurements of brachial BP were collected according to AHA recommendations. Using multivariable analysis, we assessed the association between change in LVEF and pre-existing ACC/AHA stages of hypertension (HTN) after accounting for pre-treatment LVEF, diabetes status, age, and body mass index (BMI). All analyses were performed by those blinded to all participant identifiers. Participants (n=259, female) were aged 56±11 (Mn + SD) years and were 76% white &amp; 19% black (NCT02791581 and NCT01719562). Cancer therapies included combinations of anthracyclines (23%), trastuzumab (10%), paclitaxel (22%) and cyclophosphamide (30%). After accounting for pre-treatment LVEF, diabetes status, age, and BMI, participants with stage 2 HTN experienced a significant decline (p=0.037, Figure) in LVEF relative to individuals with normal blood pressure. Conclusion: Relative to women with normal blood pressure, women with stage 2 HTN experienced a larger decline in LVEF (p=0.037) three months after initiating potentially cardiotoxic chemotherapy for breast cancer. This finding raises the possibility that lower blood pressure targets among women receiving adjuvant treatment for breast cancer may be associated with improved preservation of LVEF.
Abstract 12117: Machine Learning to Probe Variability in Patient Outcomes After Atrial Fibrillation Ablation - The Stanford AF Registry (start)
Authors: Brototo Deb, neal bhatia, Albert J Rogers, Tina Baykaner, Hui Ju Chang, Paul L Clopton, Prasanth Ganesan, Ruibin Feng, Samuel Ruiperez-Campillo, Mintu Turakhia, Alexander C Perino, Marco V Perez, Paul Zei, Nitish Badhwar, Nitish Badhwar, Chad Brodt, Sanjiv M Narayan, Paul J Wang, Mohan N Viswanathan
Journal: Circulation (2022)

Introduction: A major challenge in improving atrial fibrillation (AF) ablation is the variability in outcome between patients, which is not captured by traditional biostatistics. Hypothesis: We hypothesized that machine learning (ML) can be used to probe phenotypes of variable response to AF ablation. Methods: We studied 632 patients with drug-refractory AF, enrolled prospectively for a uniform strategy of PVI plus map-guided AF ablation at Stanford Health. We applied unsupervised ML to 64 variables to identify features associated with freedom from AF or atrial tachycardia (AT) at 3 years. Results: Patients (N=632) were 65±10 years, 28.2% female, BMI 30.2±6 kg/m2, 59.7% with non-paroxysmal AF, and 70.0% at de novo ablation. At 1-year, freedom from AF and AF/AT were 77.5% (95% CI interval: 74.2%, 80.9%) and 70.1% at 1 year (66.5%, 73.8%). At 3 years, they were 55.5% (51.2%, 60.1%) and 48.6% (44.3%-53.3%) respectively, regardless of antiarrhythmic drugs (P=0.23). Unsupervised ML revealed 3 phenotypic clusters that crossed conventional AF labels (Fig1). An Early AF cluster had best outcomes (1Y/3Y: 79.6 /53.5%); a Non-remodeled AF cluster (69.8/52.0%) had most comorbidities, a substantial number of non-paroxysmal AF patients, yet better outcomes than a cluster characterized by atrial or ventricular Remodeling (66.4/42.3%) (p=0.028) (Table 1). Conclusions: In a large prospective AF registry, ML revealed clusters for outcomes, spanning conventional clinical labels and highlighting that patients with comorbidities may have good outcomes if they lack structural remodeling, and that electrical and structural remodeling may follow independent courses between patients.
Abstract 12295: Relation Between Withdrawal of Heart Failure Therapy and Left Ventricular Function After Improvement of Cancer Therapeutics Related Cardiac Dysfunction
Authors: Nuri Lee, Kye Hun Kim, Hyukjin Park, Hyung Yoon Kim, Jae Young Cho, HyunJu Yoon
Journal: Circulation (2022)

Introduction: This study aimed to investigate withdrawal of guideline-directed medical therapy (GDMT) is associated with decline of left ventricular (LV) function after recovery from cancer therapeutics related cardiac dysfunction (CTRCD). Methods: From Mar 2015 to Dec 2021, 126 patients with improving CTRCD [defined as &gt;10% point improvement in LV ejection fraction (LVEF)] were identified. They were divided into 2 groups: patients who continued GDMT (GDMT+) and withdrew GDMT (GDMT-) after improvement of CTRCD. LV functional changes within 1 year and composite clinical outcome which was defined as hospitalization due to heart failure and all-cause death were compared between 2 groups. Results: The most frequent primary cancer was breast cancer [94 (74.6%)], followed by lymphoma [16 (12.7%)] and multiple myeloma [7 (5.6%)]. GDMT was withdrawn in 41 (32.5%) patients after improvement of CTRCD. Mean LVEF and LV global longitudinal strain (GLS) were comparable between 2 groups at the time of CTRCD diagnosis (LVEF: 44.6±8.5% in GDMT+ vs. 45.5±7.7% in GDMT-, p=0.592, LV GLS: 13.3±2.9% in GDMT+ vs. 13.6±2.7% in GDMT-, p=0.553), and when LVEF was improved (LVEF: 57.1±8.0% vs. 58.3±7.4%, p=0.457, LV GLS: 14.1±3.2% vs. 14.6±3.1%, p=0.398). Dividing into 4 groups according to LVEF at the time of CTRCD diagnosis, patients with LVEF 45-55% showed no significant difference of LV function after withdrawal of GDMT (LVEF: 65.4±3.9% vs. 63.5±4.1%, p=0.066, LV GLS: 16.9±2.2% vs. 16.2±1.8%, p=0.205), but patients with LVEF &lt;45% experienced significant decline of LVEF (LVEF: 52.7±6.4% vs. 48.7±7.2%, p=0.041, LV GLS: 11.8±2.7% vs. 11.2±2.4%, p=0.445). Withdrawal of GDMT was associated with poor composite clinical outcome in the multivariable-adjusted model [hazard ratio (95% CI) 1.38 (1.01 - 1.93), p=0.005]. Conclusions: Withdrawal of GDMT was associated with poor clinical outcome and decline of LV function in patients with improving CTRCD, particularly in patients with LVEF &lt;45%.
Abstract 12248: Decreased Left Ventricular Hemodynamic Forces As A Novel Biomarker Of Myocardial Dysfunction In Duchenne Muscular Dystrophy
Authors: Sarah E Kollar, Francesco Capuano, Michelle Udine, Jonathan Soslow, Yue-Hin Loke, Christopher Spurney
Journal: Circulation (2022)

Introduction: Patients with Duchenne muscular dystrophy (DMD) develop progressive cardiomyopathy. Cardiac magnetic resonance (CMR) imaging is used to identify global and regional function, as well as myocardial fibrosis in DMD. Unique left ventricular (LV) biomechanics cannot be assessed through conventional CMR techniques. Thus, we investigated hemodynamic force (HDF) through cine derived wall motion in the LV as a novel biomarker of myocardial dysfunction in DMD patients. Methods: This retrospective study consisted of CMR studies from DMD patients and age-matched controls. Feature-tracking (Qstrain, Medis) was performed on short-axis and long-axis cine imaging to capture LV wall motion. A novel technique based on diffeomorphic mapping was used to calculate three-dimensional LV kinematic models and HDF vectors throughout the cardiac cycle (Figure 1A). The apical-basal, lateral-septal, and anterior-posterior HDF vectors were correlated with global and regional functional parameters. Results: Eleven DMD and 11 controls were enrolled with LV EF 51 ± 6 vs 56 ± 6 (p = 0.09). DMD patients had decreased apical-basal and lateral-septal HDF across multiple points in the cardiac cycle compared to controls (Figure 1B). Six DMD patients with LV EF &lt; 55% were compared to 5 DMD patients with normal EF, demonstrating significant decrease in apical-basal systolic root mean square (RMS) HDF (p = 0.015), lateral-septal systolic RMS HDF (p = 0.009), anterior-posterior diastolic RMS HDF (p = 0.011), and magnitude systolic RMS HDF (p = 0.011) in patients with dysfunction. Absolute magnitude RMS HDF in all axes correlated with LV global longitudinal strain, LV global circumferential strain, and LV EF (r = 0.59 to 0.81, p &lt; 0.05). Conclusions: Cine derived HDF may be a more sensitive measure of LV dysfunction in DMD patients. Apical-basal HDF has potential as a novel biomarker for progression of disease.
Abstract 11922: The Independent Effects of Race/Ethnicity and Local Childhood Opportunity on Outcomes in Pediatric Congenital Heart Surgery
Authors: Mahmud Elfituri, Isabella Zaniletti, Robert W. Ressler, Clemens Noelke, Bruce Gelb, Robert Pass, Howard Seiden, Son Duong
Journal: Circulation (2022)

Background: Disparities in congenital heart disease (CHD) outcomes based on race/ethnicity and social determinants of health coexist. We sought to determine the independent effects of these factors on outcomes after pediatric CHD surgery. Methods: Pediatric Health Information System encounters age &lt;18 years from 2003-2022 with ICD9/10 codes for CHD and cardiac surgery were linked to Zip Code-level Childhood Opportunity Index (COI), a score of neighborhood educational, environmental, and socioeconomic conditions. Independent effects of race/ethnicity and COI quintile on the outcome of death during surgical hospitalization were modeled with generalized estimating equations. Survival in neonates was modeled with Cox PH regression. Results: Of 193,028 encounters at 46 centers, Black, Asian, and Other groups had increased adjusted mortality compared to Non-Hispanic (NH) White. Compared to the middle COI quintile, the lowest quintile had a higher adjusted risk of death and the highest quintile was protective (Table 1a). In survival analysis of neonates (n=47,649; median follow-up 1.1 years), Black, Asian, and “Other” groups had worse survival than NH-White even after adjustment for COI quintile (Table 1b, Figure 1). Conclusions: Black, Asian, and “Other” children have increased in-hospital death after CHD surgery independent of local opportunity. Medium-term survival after neonatal surgery is similarly influenced, suggesting local opportunity is influential even at birth. Policies to improve local social determinants of health may improve outcomes, but persistent negative effects of minority status may be explained by other unmeasured forms of structural racism.
Abstract 12263: Lack of Diversity in Aortic Stenosis Progression Cohorts: A Systematic Review
Authors: Joshua J Man, Ludovic Trinquart, Sharanya Mohanty, Benjamin S Wessler
Journal: Circulation (2022)

Introduction: Aortic stenosis (AS) is characterized by highly variable progression rates. Differential rates of AS progression have been proposed to explain apparent disparities in the treatment of severe AS. However, the evidence supporting this claim is uncertain. Methods: We conducted a systematic review of MEDLINE and EMBASE from 1989 to 2022 to identify prospective cohort studies of AS hemodynamic progression. We evaluated the pooled patient demographics, AS severity, baseline and mean annual changes in echocardiographic markers, and prognostic factors. Results: We identified 32 prospective cohort studies. Overall, 11,432 patients were followed for 27 +/- 15 months on average. The average age was 67 +/- 8 years. The average percent female was 36 +/- 14%. Race was reported in only 4 (13%) cohorts; the average proportion of white patients was 93.9 +/- 6.1%. The average baseline hemodynamic severity was consistent with aortic sclerosis, mild AS, moderate AS, and severe AS in 3 (9.4%), 8 (25.0%), 19 (59.3%), and 2 (6.3%) studies, respectively. Overall, average baseline and annual changes in echocardiographic values were: peak aortic jet velocity (Vmax) 3.21 +/- 0.61 m/s (0.20 +/- 0.09 m/s/yr); aortic valve area (AVA) 1.23 +/- 0.31 cm2 (-0.09 +/- 0.05 cm2/yr); and mean aortic valve gradient (MG) 26.2 +/- 7.6 mmHg (3.9 +/- 1.6 mmHg/yr). Age, sex, coronary artery disease, hypertension, diabetes, hyperlipidemia, and smoking were not associated with AS progression in &gt;75% cohorts. Baseline Vmax and MG were associated with greater AS progression in 6 cohorts (75%). Baseline aortic valve calcification (AVC) and AVA were consistently associated with greater AS progression in 9 cohorts (100%). One cohort found that women have a greater ΔMG for a given level of AVC. A univariate analysis of race in one cohort showed that African American ethnicity was associated with lower risk of progression from normal aortic valves to incident AS. Conclusion: There is limited representation of women and ethnic minorities in prospective AS progression cohorts. Active recruitment of diverse populations in these cohorts is needed. The available clinical evidence provides limited support for claims of differential progression as the cause of racial disparities in AS treatment.
Abstract 11999: Molecular and Cellular Characterization of RyR2 Mutations Linked to Long-QT Syndrome
Authors: Wenxuan Cai, Carmen R Valdivia, Songhua Li, Talia Booher, Jingjing Zheng, Teresa Villarreal-Molina, Norma A Balderrábano-Saucedo, Argelia Medeiros-Domingo, Pedro Iturralde, Hector H Valdivia, Francisco Alvarado
Journal: Circulation (2022)

Long-QT syndrome (LQTS) is a cardiac disorder characterized by prolonged QT interval and abnormal T waves on the electrocardiogram. Electrical abnormality can lead to severe arrhythmias, syncope and sudden cardiac death. Mutations in the Na + and K + channels or associated proteins account for the majority of cases; however, the genetic causes of about 20% of LQTS cases remain poorly understood. Recent genetic studies revealed novel LQTS-associated variants on the cardiac ryanodine receptor (RyR2), a Ca 2+ channel responsible for Ca 2+ -induced Ca 2+ release and excitation-contraction coupling. Given the important roles of RyR2 in the electrical activity of heart and previous evidence of RyR2 mutations in other inherited arrhythmias, we hypothesized that RyR2 mutations lead to functional alterations of the channels and contribute to dysregulated Ca 2+ release and pathological electrical remodeling. Eleven novel RyR2 mutations were identified in genetic studies of LQTS patients, including S166C, H877P, R1760W, G2094S, R2824W, R2920Q, R3673W, Y4287N, V4298M, P4534S and K4594Q. [3H] ryanodine (RyR2 ligand) binding assays revealed variable effects of the mutations on the opening probability of the RyR2 channel. In cell lines with stable expression of RyR2, Ca 2+ overload activates RyR2 channels and leads to spontaneous Ca 2+ release into the cytoplasm. Compared to WT RyR2, LQTS-associated RyR2 mutations cause an increase in the proportion of cells that exhibit spontaneous Ca 2+ release at various Ca 2+ concentrations, suggesting an increase in luminal Ca 2+ sensitivity of the channels. A transgenic mouse model carrying the R2920Q mutation was used to investigate the cellular and molecular pathways leading to LQTS. Homozygous mice showed prolonged QT interval and QTc at 5 months. Electrophysiological studies of the isolated cardiomyocytes revealed a depolarized resting membrane potential in the homozygous R2920Q cardiomyocytes and prolonged action potential duration in both heterozygous and homozygous R2920Q cardiomyocytes, compared to the WT cells. The availability of a mouse model that recapitulates the cardinal signs of LQTS will allow for deeper mechanistic insight into the role of RyR2 dysfunction as a driver of this arrhythmogenic syndrome.
Abstract 12439: A Systematic Review on the Management and Outcomes of Patients With Mitral Annular Calcification Thrombus
Authors: Amber Cintosun, David Belzile, Ani Orchanian-Cheff, Wendy Tsang
Journal: Circulation (2022)

Introduction: Mitral annular calcification (MAC) is a common chronic degenerative process of the mitral valve. Thrombus formation on MAC is a rare complication that is poorly understood and likely contributes to the increased risk of thromboembolic events. We performed a systematic review (PROSPERO 2022 CRD42022299281) to understand the management and outcomes of patients with thrombus on MAC. Methods: Medline, Embase, and Cochrane databases (inception to December 2021) were searched to identify studies with MAC thrombus. Patients with prior mitral valve intervention or prosthesis were excluded. The outcomes of interest were treatment, mortality, and thromboembolic events. Results: Fifteen studies with 22 cases of MAC thrombus were included (Table 1). The average age at diagnosis was 69.1±14.8 years and 82% were female. Most patients presented with stroke or transient ischemic event (68%) or myocardial infarction (18%). All patients were diagnosed with either transthoracic (82%) or transesophageal (18%) echocardiography. Seventy-seven percent of patients were treated with anticoagulation alone and 23% required surgery. The most common indication for surgery was prevention of recurrent embolization (14%). No mortality was reported. Thromboembolic events after diagnosis occurred in 27%. For those treated with anticoagulation alone, 23% had persistent thrombus with or without embolization. Conclusions: This is the first systematic review examining the management and outcomes of patients with MAC thrombus. In patients with MAC who present with a thromboembolic event, careful echocardiographic assessment of MAC to exclude the presence of thrombus should be performed. While most patients can be managed with anticoagulation alone, a significant number will require surgery. Persistent thrombus despite anticoagulation and recurrent embolization are common. Larger studies are needed to elucidate the optimal long-term care for these patients.
Use of real world data to improve drug coverage decisions in China
Authors: Wen Wang, Jing Tan, Jing Wu, Shiyao Huang, Yunxiang Huang, Feng Xie, Xin Sun
Journal: BMJ (2023)

HealtH tecHnology assessMent in cHina Use of real world data to improve drug coverage decisions in ChinaWen Wang and colleagues discuss the rationale and propose a framework for using real world evidence to support coverage decisions in Chinese setting• Policy, academic, and technical forces are becoming available to improve the quality and relevance of data available to guide coverage decisions
Abstract 13648: Risk Profile and Prognostic Implications of Premature Advanced Atherosclerotic Disease Among Young Adults: The Coronary Artery Calcium Consortium
Authors: Ellen Boakye, Zeina A Dardari, Ngozi Osuji, John Erhabor, Olufunmilayo Obisesan, Albert Osei, Omar Dzaye, Kunal Jha, Alan Rosanski, Daniel S Berman, Matthew Budoff, Michael D Miedema, Khurram Nasir, John A Rumberger, Leslee J Shaw, Michael J Blaha
Journal: Circulation (2022)

Introduction: Advanced atherosclerotic disease among young adults is an under-recognized and unique disease phenotype that has not been well characterized. Methods: We used data from 23,706 participants aged 30-50 years (mean age 43.9 ± 4.6 years; 74.7% men) from the Coronary Artery Calcium (CAC) Consortium, a cohort of individuals with no prior CVD history referred for CAC scanning. We defined advanced disease as CAC ≥ 90 th percentile for age, sex, and race, and compared risk factor profile of persons with advanced disease to those without CAC and those with CAC &lt; 90 th percentile. Using multivariable-adjusted Cox proportional hazard and competing risks regression, we assessed the association of advanced disease with all-cause, cardiovascular (CV), and CHD mortality. Results: Of the 23,706 participants, 8,289 (35%) had CAC. Among them, 3,549 (43%) had CAC ≥ 90 th percentile. Compared to persons without CAC and those with CAC &lt; 90 th percentile, those with CAC ≥ 90 th had higher prevalence of all the traditional CVD risk factors. Notably, 56% of those with CAC ≥ 90 th percentile had ≥ 2 risk factors, and 68% already had multivessel CAC compared to 34% of those with CAC &lt; 90 th percentile. After a mean follow-up of 12.6 ± 3.6 years, the incidence of all-cause, CV, and CHD mortality was highest in those with advanced disease. Persons with CAC ≥ 90 th percentile had a higher multivariable-adjusted risk of all-cause (HR 2.11 [1.62 - 2.73]), CV (SHR 2.88 [1.74 - 4.78]), and CHD mortality (SHR 4.41 [2.16 - 8.98]), compared to those without CAC. When compared to those with CAC &lt; 90 th percentile, only those with CAC ≥ 90 th percentile had significantly higher risk of all-cause, CV, and CHD mortality ( Figure ). Conclusions: Premature advanced atherosclerosis is a distinct clinical phenotype that strongly predicts all-cause and cause-specific mortality. Among persons with CAC at young age, those with scores ≥ 90th percentile have the highest risk of early death and should be a focus of clinical prevention.
Abstract 13630: Association Between Arrhythmia Burden During Clinical Exercise Testing and All-Cause Mortality
Authors: Jenna L Taylor, Jose R Medina-Inojosa, Audry Chacin Suarez, Betsy J Medina-Inojosa, Virend K Somers, Amanda R Bonikowske
Journal: Circulation (2022)

Introduction: Arrhythmias commonly occur during clinical exercise stress testing (EST), however there are limited data on prognostic significance, particularly differences between individuals with minor versus significant arrhythmia burden. Hypothesis: We hypothesized that significant but not minor arrhythmia burden during EST would be predictive of future all-cause mortality. Methods: Adults who underwent clinically indicated EST at Mayo Clinic Rochester between September 1993 and April 2017 were included and followed-up until March 2021 using the National Death Index to ascertain survival status. Expert clinician coding pertaining to arrhythmia burden during EST were used to group individuals (see Table 1 ). Cox proportional hazard models adjusted for known predictors of exercise-induced arrhythmias, were used to test the association of arrhythmia burden with all-cause mortality. Results: A total of 30796 individuals were included (age: 55±14yrs; female: 36%; Table 1 ). Mean follow-up was 8.8±3.6yrs, with a total of 2516 deaths. Arrhythmia during EST was associated with all-cause mortality compared with no arrhythmia (HR: 1.72; 95% CI: 1.58-1.88; p&lt;0.001), however significant arrhythmia showed greater association compared with minor arrhythmia (HR: 2.07; 95% CI: 1.81-2.38; p&lt;0.001). Both minor and significant arrhythmia during EST were significant predictors of all-cause mortality compared with no arrhythmia ( Figure, Table 2 ), however, after model adjustments, only significant arrhythmia was associated with all-cause mortality (HR: 1.40; 95% CI: 1.21-1.63; p&lt;0.001) ( Table 2 ). Conclusions: After multivariate adjustment, significant arrhythmia burden during EST showed a 40% increased future risk of all-cause mortality, Conversely, adjusting for age and sex attenuated the effect of minor arrhythmia burden during EST on incidence of death. These results highlight the clinical significance of arrhythmia burden during exercise testing.